Sulfonamide derivatives containing dihydropyrazole moieties selectively and potently inhibit MMP-2/MMP-9: Design, synthesis, inhibitory activity and 3D-QSAR analysis.
Bioorg Med Chem Lett
; 25(20): 4664-71, 2015 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-26346367
New series of sulfonamide derivatives containing a dihydropyrazole moieties inhibitors of MMP-2/MMP-9 were discovered using structure-based drug design. Synthesis, antitumor activity, structure-activity relationship and optimization of physicochemical properties were described. In vitro the bioassay results revealed that most target compounds showed potent inhibitory activity in the enzymatic and cellular assays. Among the compounds, compound 3i exhibited the most potent inhibitory activity with IC50 values of 0.21 µM inhibiting MMP-2 and 1.87 µM inhibiting MMP-9, comparable to the control positive compound CMT-1 (1.26 µM, 2.52 µM). Docking simulation was performed to position compound 3i into the MMP-2 active site to determine the probable binding pose. Docking simulation was further performed to position compound 3i into the MMP-2 active site to determine the probable binding model the 3D-QSAR models were built for reasonable design of MMP-2/MMP-9 inhibitors at present and in future.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirazoles
/
Sulfonamidas
/
Diseño de Fármacos
/
Metaloproteinasa 2 de la Matriz
/
Metaloproteinasa 9 de la Matriz
/
Relación Estructura-Actividad Cuantitativa
/
Inhibidores de la Metaloproteinasa de la Matriz
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2015
Tipo del documento:
Article
Pais de publicación:
Reino Unido